Usefulness of Coronary Computed Tomography Angiography For Early Triage of Patients with Acute Chest Pain - The Rule Out Myocardial Infarction Using Computer.

Usefulness of Coronary Computed Tomography Angiography For Early Triage of Patients with Acute Chest Pain - The Rule Out Myocardial

Infarction Using Computer Assisted Tomography (ROMICAT) Trial

Udo Hoffmann, Fabian Bamberg, Claudia U. Chae, John H. Nichols, Ian S. Rogers, Sujith K. Seneviratne, Quynh A. Truong, Ricardo C. Cury, Suhny Abbara, Michael D. Shapiro, Jamaluddin Moloo, Javed

Butler, Maros Ferencik, Hang Lee, Ik-Kyung Jang, Blair A. Parry, David F. Brown, James E. Udelson, Stephan Achenbach, Thomas J.

Brady, John T. Nagurney

Department of Radiology, Emergency Medicine, and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston MA

Research Grants: Siemens Medical Solutions, Amersham/GE Healthcare, Bracco Diagnostics, NIHAdvisory Boards: Vital Images, Bayer Healthcare/Siemens Medical Solutions

Disclosures

Early Risk Stratification and Triage in the ED

- 6 Million present with chest pain to ED annually- - ECG, initial biomarkers, and clinical presentation and traditional risk factors – no safe triage possible (Nagurney, JAMA 2006)

- low threshold to admit, >80% have no ACS, $8Billion annually healthcare cost

- 1-5% of missed ACS cause 20% of ED malpractice costs

Improvement of the initial ED evaluation needed!

Preliminary coronary CTA Studies

- coronary MDCT is feasible in the acute care setting

- low to intermediate risk patients - absence of CAD has 100% NPV for ACS – found in 40% of patientsHoffmann et al Circulation 2006

- very low risk patients - CT may be cost saving alternative to myocardial perfusion stress testing Raff et al JACC 2007

- normal coronary CTA has excellent NPV for MACE within 15 months Rubinshtein et al. Circulation 2007

Remaining Questions for Patient Management

1. Confirmation in larger cohorts

2. Safety of Stenosis based Triage

3. Relevance of detected Stenosis

4. Incremental Value of non-calcified plaque for exclusion of ACS

ROMICAT I - Specific Aims

1. Determine the prevalence of coronary atherosclerotic plaque and stenosis in patients with acute chest pain and low to intermediate for ACS

2. Determine the diagnostic accuracy of these findings for ACS

3. Determine whether this information is incremental to current risk assessment

ED tAcute Chest Pain

Neg. ECG

Neg. Trop

Index Hospitalization

Observational, double-blinded Cohort Study

Cardiac CT Analysis - blinded to caregiver and subjects

1. Presence of atherosclerotic plaque per coronary segmenta. Calcified plaqueb. Non-calcified plaque

2. Presence of significant coronary artery stenosis (>50%)

6 month FUStandard clinical care

ROMICAT I – Study Design

Inclusion Criteria- >5 min of chest pain <24h- Normal initial Biomarker- Admitted to Rule out MI- Normal sinus rhythm

Exclusion Criteria

- positive initial Troponin

- Diagnostic ECG changes

- Creatinine >1.3 mg/dl

- Known CAD

Primary Endpoint

ACS* (NSTEMI or UAP) during Index Hospitalization and MACE during 6-month follow-up adjudicated by independent committee

*According to AHA/ACC/ESC Guidelines

ROMICAT I - Methods

Coronary MDCT- 64-slice MDCT (Siemens, Forchheim, Germany)- Beta-Blocker if HR>65 bpm, Nitro- ~20 ml + 80ml contrast agent (Iodhexodol 320)- tube current: ~850 mAs, tube voltage: 120 kV

Protocol Eligible Subjects (n = 658)

Enrolled Subjects (n = 412)

Study Population (n = 368)

• Physician Denied (n = 19)• Patient Refusal (n = 124)• Missed to Ongoing Recruitment (n = 103)

Incomplete Scan (n=17)• Interference with Clinical Care (n = 10)• Claustrophobia/Nausea (n = 3)• Contrast Extravasation (n = 3)• Scanner Malfunction (n = 1)

Complete Scan (n=27)• History of Stent Placement (n = 10)• History of CABG (n = 17)

18 month Screening and Enrollment

ROMICAT I – Demographics and Risk Factors

Age (years, mean SD) 52.7±12

Male Gender (n, %) 223 (61%)

Race (n, %) African American Caucasian Asians Others

31 (8%)313 (85%)

4 (1%)20 (6%)

No. of risk factors (median, IQR) 2 (1)

TIMI Score (low/intermediate/high) in %

94.3/ 5.4/ 0.3

ACS during index hospitalization (%, n) Unstable angina pectoris (%, n) Myocardial infarction (%, n)

31 (8%)23 (74%)8 (26%)

MACE during six month follow- up (%, n):Recurrent chest pain:

Outpatient evaluation (PCP)Readmission without testingReadmission with testing

068 (18%)50 (74%)

5 (7%)13 (19%)

ROMICAT I – Prevalence of Plaque and Stenosis

No CAD - 50.4% (no plaque and no

stenosis)N= 185/368

Significant stenosis detected or not excluded -

18.4%N= 68/368

Non-obstructive Plaque - 31.2%

N= 115/368

CAD categories with relevance for early triage of patients with ACP in the ED

ROMICAT I – CAD and ACS

No CAD

Nonobstructive Plaque

Significant stenosis detected or not excluded

No ACS

7 ACS• non-stenotic ACS• small vessel disease

24 ACS

NSTEMI with significant stenosis

40-year old male who presented 3 hours after the onset of substernal chest pain, inconclusive initial evaluation in the ED, Troponin positive 8 hours after ED presentation, underwent invasive coronary angiography with stenting of an 80% mid LAD

NSTEMI without significant stenosis in CT

Subject Coronary CTA Finding of Non-obstructive

Plaque

Troponin Stress Nuclear Perfusion Imaging

Coronary Angiography/ Intervention

Clinical Outcome

76-year old female

prox RCA, prox LCX, and prox and mid LAD

Negative inferolateral area of ischemia

None UAP

78-year old female

LM, prox, mid, and dist. LAD; PDA

Negative inferolateral area of ischemia

None UAP

72-year old male

Mid RCA Negative apical area of ischemia, hypokinesis inferolateral region

None UAP

52-year old male

Mid LAD 2nd set pos. (+6.8h)

None 30% stenosis in mid LAD/None

NSTEMI

63-year old male

Prox and mid RCA, mid and dist. LAD

3rd set pos. (+5.7h)

None 95% PLV, 50% 1st septal branch/ stent

PLV

NSTEMI

53-year old male

LM and dist. LAD 2nd set pos. (+6.6h)

None 40% D2 ostium, 70% D3 ostium stenosis/None

NSTEMI

59-year old female

OM1 Negative None 80% PDA stenosis/ stent PDA

UAP

Subject Coronary CTA Finding of Non-obstructive

Plaque

Troponin Stress Nuclear Perfusion Imaging

Coronary Angiography/ Intervention

Clinical Outcome

76-year old female

prox RCA, prox LCX, and prox and mid LAD

Negative inferolateral area of ischemia

None UAP

78-year old female

LM, prox, mid, and dist. LAD; PDA

Negative inferolateral area of ischemia

None UAP

72-year old male

Mid RCA Negative apical area of ischemia, hypokinesis inferolateral region

None UAP

52-year old male

Mid LAD 2nd set pos. (+6.8h)

None 30% stenosis in mid LAD/None

NSTEMI

63-year old male

Prox and mid RCA, mid and dist. LAD

3rd set pos. (+5.7h)

None 95% PLV, 50% 1st septal branch/ stent

PLV

NSTEMI

53-year old male

LM and dist. LAD 2nd set pos. (+6.6h)

None 40% D2 ostium, 70% D3 ostium stenosis/None

NSTEMI

59-year old female

OM1 Negative None 80% PDA stenosis/ stent PDA

UAP

NSTEMI with small vessel disease

59-year old female with typical chest pain, non-diagnostic ECG and negative serial Troponin, coronary CTA – plaque in OM 1, invasive coronary angiography demonstrates 95% stenosis of the PDA

NSTEMI with PDA stenosis

ROMICAT I – Diagnostic Accuracy

Sens: 100% (0.88-1.00)

NPV: 100% (0.98-1.00)

Spec: 54% (0.49-0.60)

PPV: 17% (0.12-0.23)

ACSNo

ACS

Plaque

No Plaque

31 154

0 183

Sens: 77% (0.59-0.90)

NPV: 98% (0.95-0.99)

Spec: 87% (0.82-0.90)

PPV: 35% (0.24-0.48)

ACSNo

ACS

Sign. Stenosis

No Stenosis

24 44

7 293

1. Triage Criterion: Presence of any plaque

2. Triage Criterion: Presence of significant Stenosis (>50%)

Results – Stenosis and ACS

• specificity of significant stenosis for ACS was lower in subjects ≥65 years of age (58% vs. 91%) because of increased prevalence of CAC (84% vs. 39%; p<0.0001)

• in 34 patients a significant stenosis was detected• 20 had ACS• 14 had no ACS or MACE after 6 months

severe RCA lesion, no regional LV dysfunction, normal stress SPECT study,diagnosis of ‘non cardiac chest pain’.

Incremental Value of coronary CTA to TIMI

AUC for the detection of ACS during index hospitalizationExtent of plaque, presence of stenosis, TIMI risk score (AUC: 0.88, 0.82 vs. 0.63; respectively, all p<0.0001).

Summary

- confirmation - Absence of any CAD in 50% of patients - 100% NPV for ACS – may enable early safe and early discharge from the ED

- triage criterion of 50% stenosis is not perfect because of non-stenotic ACS and limited spatial resolution of coronary CTA

- significant stenosis is detected in 10% of patients by coronary CTA – about 40% of these were discharged with a diagnosis of non-cardiac chest pain

- incremental value of non- calcified plaque for early triage is limited

Thank you!

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